Alterations in plasma and brain amino acids after administration of the glycine/NMDA receptor partial agonist, D-cycloserine, to mice and rats.

The NMDA/glycine receptor partial agonist, D-cycloserine, has recently been reported to exert anticonvulsant effects in different seizure models in mice and rats. In view of the high doses (> 100 mg/kg) needed for these effects, actions other than those mediated by the glycine site might be involved. In this respect, inhibition of pyridoxal phosphate-dependent enzymes involved in amino acid metabolism might play a role. In the present experiments, D-cycloserine was administered at an anticonvulsant dose (320 mg/kg) to mice and rats and levels of 11 amino acids, including several neurotransmitters, were determined in brain cortex and plasma at different times after administration. In addition, the concentration of D-cycloserine was determined in plasma and brain. Compared to peak concentrations of D-cycloserine in plasma, only about 20% of D-cycloserine appeared in the brain. The only marked alteration in brain amino acids was an increase in alanine levels, while amino acids acting as neurotransmitters were hardly altered. The data indicate that the anticonvulsant action of D-cycloserine is not secondary to changes in levels of amino acid neurotransmitters.